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Antinociceptive and neurotoxic effects of opioids
Moravcová, Radka ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
2. Abstract The curative actions of opioids have been known over two millenia. However, the mechanisms of their analgesic effects were only decoded in the last 20 years. There are 3 main types of opioid receptors (µ, κ, δ), that are together with the opioid peptidic system involved in antinociceptive processes and are widespread in the nervous system. Calcium plays a very important role in the pain perception and antinociception. Changes in its concentration are crucial for the neurotransmitter release. The relationship between the analgetic actions of opioids and the availability of Ca2+ in the CNS is explained in the way that, decreasing extracellular concentration of Ca2+ and/or by passaging through the membrane, antinociception will increase. Opioid analgesic effects are limited by their relatively high ability to create tolerance or addiction. Since these effects only result from heavy doses and long-term usage, severe complications should not arise during the right usage of these drugs. However, opioids can also have neurotoxic effects. The opioid-induced toxicity occurs in case when opioids release toxic metabolites during the process of their degradation in the liver. The neurotoxicity can be induced by the oxidation of the double bond in the opioid's chemical structure, thus producing free radicals...
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Genetic changes in the regulatory regions of NMDA receptors and their association possible connection the development of schizophrenia
Hrychová, Šárka ; Balík, Aleš (advisor) ; Moravcová, Radka (referee)
Schizophrenia is a serious neuropsychiatric disorder with a severe impact on patients' lives. Based on the experiments in animal models and also from the observations of the influence of the drug in humans it was concluded that the decreased activity of N-methyl-D- aspartate (NMDA) receptor gives rise to behaviour that is associated with the clinical manifestation of schizophrenia. Therefore, it is hypothesized that genetically determined variations in NMDA receptor activity contributes to the emergence and development of schizophrenia. The aim of this bachelor thesis is to summarize current knowledge on genetic alternations particularly in the regulatory regions of NMDA receptors in schizophrenia. Key words: schizophrenia, NMDA receptor, genetic changes
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Circadian system in mitochondria
Šemíková, Johana ; Bendová, Zdeňka (advisor) ; Moravcová, Radka (referee)
The rhythms of circadian clocks throughout our bodies are not governed only by the light/dark cycle, but in many peripheral tissues circadian clocks are reset based on availability of nutrients and timing of food intake. The circadian system responds to changes in the levels of two metabolites (AMP and NAD+ ) that are central to biochemical reactions involved in energy production, storage, and utilization through the metabolic sensors AMPK and SIRT1. The aim of this review is to summarize mechanisms for energetic metabolism known to date that are connected with the regulation of circadian rhythms and explain their function in maintaining their stability. Last but not least, to show possible dysregulation of these mechanisms and their impact on the circadian system.
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Beta-adrenergic signaling in the rat myocardium under long-term morphine treatment
Moravcová, Radka ; Novotný, Jiří (advisor) ; Roubalová, Lenka (referee)
2. Abstract The aim of this dissertation was to evaluate the effect of low doses (0,1 mg/kg, 1 mg/kg, 1 mg/kg per day for 28 days + 7 days of abstinence) and high doses (10 mg/kg per day for 10 days) of morphine on transmembrane signaling mediated by G-protein coupled receptors (GPCRs) in the rat myocardium. Opioid receptors (OR) and mainly β-adrenergic receptors (β-AR) belong to the most important receptors of this receptor family. δ-OR and κ-OR are the most numerous OR in the myocardium. Results of the present work indicated that there are no significant changes in the expression of these two receptor subtypes after any studied doses of morphine. There are three subtypes of β-AR (β1-AR, β2-AR and β3-AR) represent in the myocardial tissue. Here we studied the expression of β1-AR and β2-AR, because these two major subtypes of β-AR regulate through their signaling pathways functioning of the cardiovascular system. Our immunoblot analysis did not reveal any changes in the expression of β1-AR, but the expression of β2-AR was significantly decreased after treatment with morphine at the dose of 10 mg/kg for the 10 days. More sensitive saturation binding experiments with the nonselective β-antagonist [3 H]CGP 12177 indicated a significant increase in specific binding after treatment with morphine (1 mg/kg/day for...
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Antinociceptive and neurotoxic effects of opioids
Moravcová, Radka ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
2. Abstract The curative actions of opioids have been known over two millenia. However, the mechanisms of their analgesic effects were only decoded in the last 20 years. There are 3 main types of opioid receptors (µ, κ, δ), that are together with the opioid peptidic system involved in antinociceptive processes and are widespread in the nervous system. Calcium plays a very important role in the pain perception and antinociception. Changes in its concentration are crucial for the neurotransmitter release. The relationship between the analgetic actions of opioids and the availability of Ca2+ in the CNS is explained in the way that, decreasing extracellular concentration of Ca2+ and/or by passaging through the membrane, antinociception will increase. Opioid analgesic effects are limited by their relatively high ability to create tolerance or addiction. Since these effects only result from heavy doses and long-term usage, severe complications should not arise during the right usage of these drugs. However, opioids can also have neurotoxic effects. The opioid-induced toxicity occurs in case when opioids release toxic metabolites during the process of their degradation in the liver. The neurotoxicity can be induced by the oxidation of the double bond in the opioid's chemical structure, thus producing free radicals...
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